1. Field of the Invention
The present invention relates to a compound useful as a two-photon tracer, a method for the preparation thereof, a method for the visualization of intracellular glucose uptake using the same, a method for the diagnosis of cancer using the same, and a method for screening anticancer agents using the same.
The present application claims priority from Korean Patent Application No. 10-2009-0084068 filed on Sep. 7, 2009 in the Korean Intellectual Property Office, the disclosure of which is incorporated herein by reference in its entirety.
2. Description of the Related Art
Glucose is a principal energy source essential for cell growth. Fast-growing cancer cells exhibit a high rate of glycolysis; hence, the rate of glucose uptake is faster in these cells, primarily due to overexpression or enhanced intracellular translocation of glucose transporters (GLUTs) and increased activity of mitochondria-bound hexokinases in the tumor. To monitor glucose metabolism in living systems, a variety of tracers, a variety of tracers, such as [18F]-2-fluoro-2-deoxyglucose (18FDG), 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-2-deoxy-D-glucose (2-NBDG), and IR dye. 800CW-2DG, have been developed. FDG is widely used in the in vivo analysis of glucose metabolism by positron emission tomography (PEG), whereas 2-NBDG and IR dye 800CW-2DG are fluorescent probes that have been used for studying cellular metabolic functions involving GLUTs and in tumor-imaging studies.

Recently, the present inventors developed a new fluorescent probe, cyanine-3-linked O-1-glycosylated glucose (Cy3-Glc-α), which is a better glucose probe than 2-NBDG because it can be used, without glucose starvation, to produce a much brighter image, and can be applied to the screening of anticancer agents.

In one-photon microscopy (OPM), the probes are excited with short-wavelength light (˜350-550 nm); this, however, limits their applications in tissue imaging, owing to inherent problems such as shallow penetration depth (<80 μm), interference by cellular autofluorescence, photobleaching and photodamage. To overcome these problems, it is crucial to use two-photon microscopy (TPM), which utilizes two near-infrared photons for excitation. TPM offers a number of advantages over one-photon microscopy (OPM), including greater penetration depth (>500 μm), localized excitation, and longer observation times. In particular, the extra penetration depth afforded by TPM is an essential element for application in tissue-imaging studies because the artifacts arising from surface preparation, such as damaged cells, can extend over 70 μm into the tissue interior. However, visualization of glucose uptake by living cells and tissues with two-photon (TP) tracers has not been reported so far.